This invention relates to novel methods of producing the racemate and enantiomers of 9-fluoro-3-methyl-10-substituted amino-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid compounds (A) and to compounds useful as intermediates in the production of the above benzoxazine-6-carboxylic acid compounds.
It is known that the racemate 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de], 1,4-benzoxazine-6-carboxylic acid (i.e. compounds of formula A wherein Z is N-methyl piperazinyl) exhibits antibacterial properties as described in European patent application Ser. No. 47,005 and in Japanese Application No. 82 46,986. ##STR2##
Ofloxacin, a compound of formula (A) wherein Z is N-methyl piperazinyl and R.sub.1 =H, can be prepared in accordance with the following reaction scheme as described in Drugs of the Future, Vol. 8, No. 5, pages 395 and 396, (1983). ##STR3##
Using the above preparative procedure, the reductive cyclization of (IV) with H.sub.2 over RaNi in ethanol produces only the racemate (R,S) 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine (V) and hence this leads to the production of the racemate (R,S) compounds only.
In pharmacology, one enantiomer of a biologically active racemic mixture may possess biological activity, while another enantiomer of the same compound has little or no such activity. Sometimes one enantiomer possesses a certain undesirable side effect while the other enantiomer does not. Hence, an efficient route that can produce optically pure enantiomers is desirable.